The proposed work is concerned with an investigation of the effects of protein-synthesis inhibition on the transport of lipids and lipoproteins by the intestine and liver. The objective of modifying lipid transport and of determining the pathological effects on cells of altered lipoprotein formation is the information it will provide in understanding the normal mechanisms by which subcellular organelles and biochemical processes are integrated in the normal transport and secretion of lipids. Furthermore, an analysis of these processes using correlative ultrastructural biochemical and immunochemical techniques can provide needed information concerning the role of specific lipoproteins in intestinal and hepatic lipid transport and the effects on the cell of interfering with the normal function of these lipoproteins. In these studies the effects of puromycin and orotic acid on intestinal lipid transport and on lipoprotein production will be investigated. The role of lipoproteins in the transport of endogenous and exogenous lipids will be studied and the hormonal control of intestinal lipoprotein synthesis will be investigated. Other experiments will deal with possible sex differences in the pathogenesis of experimental fatty liver. The long-term objective of all of these studies is not merely the definition of the normal physiological processes involved in lipid transport but an understanding of the normal control mechanisms involved in lipoprotein production and the effects of modifying or modulating these controls in order to better appreciate human derangements in lipoprotein metabolism. This is of importance in understnading the pathogenesis of atherosclerotic disease and fatty liver and may provide clues as to rational forms of therapy.